Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The neurohypophysis comprises the nerve terminals of hypothalamic neurosecretory cells, which contain arginine vasopressin (AVP) and oxytocin. The secretory terminals of rat neurohypophyses were acutely dissociated. The macroscopic calcium currents (ICa) of these isolated peptidergic terminals were studied using 'whole-cell' patch-clamp recording techniques. 2. There are two types ('Nt' (where the subscript 't' denotes terminal) and 'L') of high-threshold voltage-activated ICa in the terminals, which can be distinguished by holding at different potentials i.e. -90 and -50 mV. Replacement of Ca2+ in the bathing solution by Ba2+ increased the amplitude of ICa, primarily due to an increase in the L-type component. Both inward currents were eliminated by adding 50 microM-Cd2+ or when in a Ca(2+)-free bathing solution. 3. omega-Conotoxin GVIA (omega-CgTx) has been widely used as a Ca2+ channel blocker. However, whether this toxin can discriminate between different types of Ca2+ channels is still a subject of controversy. We applied omega-CgTx over a wide range of concentrations (0.01-2 microM) to examine its effects on both Nt- and L-type ICa in these terminals. At a concentration of 30 nM, omega-CgTx selectively reduced, by 48%, the amplitude of Nt-type ICa. In contrast, a higher concentration (300 nM) of omega-CgTx was necessary to inhibit the L-type ICa. 4. omega-CgTx inhibited both Nt- and L-type ICa in a dose-dependent manner, and the half-maximum inhibition (IC50) of the ICa by the toxin was 50 and 513 nM, respectively, which was approximately a tenfold difference. The reduction in both types of currents did not result from any shift in their current-voltage or steady-state inactivation relationships. 5. In contrast, omega-CgTx, at a concentration of 300 nM, had no effect on the tetrodotoxin-sensitive sodium current (INa) of the isolated peptidergic nerve terminals. Furthermore, omega-CgTx did not reduce the long-lasting, non-inactivating ICa in the isolated non-neuronal secretory cells of the pars intermedia (PI) (intermediate lobe of the pituitary). 6. Our studies suggest that omega-CgTx might exert specific blocking effects on both Nt- and L-type Ca2+ channels, but that in the isolated peptidergic nerve terminals, the Nt-type component is more susceptible to this toxin.
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PMID:Two types of high-threshold calcium currents inhibited by omega-conotoxin in nerve terminals of rat neurohypophysis. 132 66

Cytosolic aminopeptidase P was obtained in highly purified form from human leukocytes by a four-step procedure. Buffy coats were the starting material. A M(r) of 140,000 was obtained by size-exclusion HPLC for the native enzyme. As shown by SDS/PAGE under reducing and denaturing conditions, the enzyme consisted of likely identical subunits with M(r) of 71,000. Purified aminopeptidase P cleaved off, specifically and efficiently, the N-terminal residues from peptides with N-terminal Xaa-Pro sequences. The penultimate proline was not replaceable by hydroxyproline, alanine and glycine in di-, tri- and tetrapeptides. Polyproline was not hydrolyzed. Dipeptides were cleaved (Arg-Pro, Phe-Pro > Trp-Pro > Pro-Pro) although slower than longer peptides. Cleavage was observed of several biologically active peptides; C-terminal fragment (residues 201-206) of C-reactive protein, oxytocin fragment Tyr-Pro-Leu-Gly, morphiceptin, peptide Gly-Pro-Arg-Pro (inhibitor of fibrin polymerization) and kentsin. In addition, cleavage of a protein, interleukin-6, was also demonstrated. Aminopeptidase P was maximally activated by Mn2+, and to a lesser extent by Co2+. The activity was optimal at pH 8. Ni2+, Zn2+ and especially Cd2+ caused marked inhibition. EDTA, 1,10-phenantroline and dithiothreitol were also inhibitory. Carbobenzoxy-phenylalanine, as well as several N-carbobenzoxy-proline-containing peptides, caused partial inhibition. The observed resistance of Gly-Pro, Pro-Gly, Pro-Phe and Pro-Ile to hydrolysis by the purified enzyme strongly indicates absence of known proline-specific dipeptidases in the aminopeptidase-P preparation.
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PMID:Aminopeptidase P from human leukocytes. 144 89

We have compared the response of proton and water transport to oxytocin treatment in isolated frog skin and urinary bladder epithelia to provide further insights into the nature of water flow and H+ flux across individual apical and basolateral cell membranes. In isolated spontaneous sodium-transporting frog skin epithelia, lowering the pH of the apical solution from 7.4 to 6.4, 5.5, or 4.5 produced a fall in pHi in principal cells which was completely blocked by amiloride (50 microM), indicating that apical Na+ channels are permeable to protons. When sodium transport was blocked by amiloride, the H+ permeability of the apical membranes of principal cells was negligible but increased dramatically after treatment with antidiuretic hormone (ADH). In the latter condition, lowering the pH of the apical solution caused a voltage-dependent intracellular acidification, accompanied by membrane depolarization, and an increase in membrane conductance and transepithelial current. These effects were inhibited by adding Hg2+ (100 microM) or dicyclohexylcarbodiimide (DCCD, 10(-5) M) to the apical bath. Net titratable H+ flux across frog skin was increased from 30 +/- 8 to 115 +/- 18 neq.h-1.cm-2 (n = 8) after oxytocin treatment (at apical pH 5.5 and serosal pH 7.4) and was completely inhibited by DCCD (10(-5) M). The basolateral membranes of the principal cells in frog skin epithelium were found to be spontaneously permeable to H+ and passive electrogenic H+ transport across this membrane was not affected by oxytocin. Lowering the pH of the basolateral bathing solution (pHb) produced an intracellular acidification and membrane depolarization (and an increase in conductance when the normal dominant K+ conductance of this membrane was abolished by Ba2+ 1 mM). These effects of low pHb were blocked by micromolar concentrations of heavy metals (Zn2+, Ni2+, Co2+, Cd2+, and Hg2+). Lowering pHb in the presence of oxytocin (50 mU/ml) produced a transepithelial current (3 microA.cm-2 at pHb 5.5) which was blocked by 100 microM of Hg2+, Zn2+, or Ni2+ at the basolateral side, and by DCCD (10(-5) M) or Hg2+ (100 microM) from the apical side. The net hydroosmotic water flux (JH2O) induced by oxytocin in frog bladder sacs was blocked by inhibitors of H(+)-adenosine triphosphatase (ATPase). Diethylstilbestrol (DES 10(-5) M), oligomycin (10(-8) M), and DCCD (10(-5) M) prevented JH2O when present in the lumen. These effects cannot be attributed to inhibition of metabolism since cyanide (10(-4) M), or 2-deoxyglucose (10(-3) M) had no effect on JH2O.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Common channels for water and protons at apical and basolateral cell membranes of frog skin and urinary bladder epithelia. Effects of oxytocin, heavy metals, and inhibitors of H(+)-adenosine triphosphatase. 164 38

Previously (Van Driessche et al. 1987) we showed that small inward (mucosa towards serosa) oriented short-circuit currents (Isc) were recorded through the toad urinary bladder when the mucosal side was exposed to Ca2+ free solutions containing K+, Na+ (+ amiloride), Cs+ or Rb+ as main cation. This current component is inhibitable by micromolar concentrations of mucosal La3+ and divalent cations (Ca2+, Cd2+) and is considerably elevated by oxytocin (0.1 U/ml). The present study demonstrates that the addition of 50 nmol/l Ag+ to the mucosal medium during oxytocin treatment caused an additional large increase of the La3+-sensitive Isc component. The power density spectrum of the fluctuation in current contained a Lorentzian component which was enhanced by oxytocin treatment. The Lorentzian component disappeared as a consequence of the administration of mucosal Ag+. In experiments with Ca2+, Ba2+ or Mg2+ as principal mucosal cation, the La3+-sensitive Isc component was negligible under control conditions and during oxytocin treatment. Mucosal Ag+ (40 nmol/l) elicited a large inward oriented current which was blockable by the calcium channel blockers, La3+ and Cd2+. Also the organic calcium entry blockers, nicardipine and verapamil (10 mumol/l) depressed the inward current considerably. Noise analysis of the currents carried by divalent cations showed a La3+-sensitive noise component. Oxytocin-Ag+ activated currents could not be recorded in the absence of the divalent cations or small inorganic cations, e.g. with solutions which contained N-methyl D-glucamine (NMDG) as main mucosal cation.
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PMID:Ca2+ channels in the apical membrane of the toad urinary bladder. 244 54

1. Isolated neurosecretory nerve endings were prepared from rat neurohypophyses. The amount of vasopressin (AVP) and oxytocin released was measured by radioimmunoassay. 2. The amount of hormone release under resting conditions was not affected by external calcium (Ca2+o). Secretion decreased by ca. 50% when external sodium (Na+o) was replaced by choline or sucrose. 3. Ouabain did not modify the basal AVP release. 4. The Na+ ionophore monensin increased the release of AVP only in the presence of Na+o. This increase was maintained during prolonged exposure to the ionophore and occurred in the presence of Ca2+o only. 5. In the presence of Ca2+o, the amount of evoked hormone release was dependent on the external K+ concentration. Half-maximal activation was achieved with ca. 40 mM-K+. The K+-induced secretion was potentiated in Na+-free solution. 6. Prolonged 100 mM-K+-induced depolarization in the presence of Ca2+o gave rise to a large increase in hormone secretion which decreased with time (t1/2 = 2.5 min). The release could be reactivated after permeabilization of the nerve terminals in the presence of micromolar concentrations of Ca2+. 7. A stepwise paradigm in which Ko+ is incrementally increased to 25, 50, 75 and then 100 mM released more AVP than a prolonged exposure to 100 mM-K+. 8. Veratridine increased the amount of AVP released. This effect was considerably reduced in the absence of Nao+ and abolished in the presence of D600. 9. The depolarization-induced AVP release was blocked by different Ca2+-antagonists. Their effectiveness was nitrendipine = nicardipine greater than Cd2+ greater than Gd3+ greater than Co2+ = Mn2+. 10. The dihydropyridine Bay K 8644 potentiated both the basal and the K+-evoked AVP release. Its maximal effect was obtained with 25-50 mM-Ko+. 11. In conclusion, the isolated neurohypophysial terminals which have both Na+ and Ca2+ channels and release AVP and oxytocin upon depolarization might be an excellent system to study further the mechanisms leading to secretion of neurohormones.
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PMID:Hormone release from isolated nerve endings of the rat neurohypophysis. 245 Sep 99

1. Single neurohypophyses from male rats were maintained in an in vitro perifusion chamber. Ion-sensitive microelectrodes were introduced into the tissue to measure changes in [K+]o and [Ca2+]o during electrical stimulation. 2. Electrical stimulation at 6 Hz for 1 min and 30 Hz for 12 s raised [K+]o by 5.4 +/- 0.4 and 13.5 +/- 0.5 mM (mean +/- S.E.M., n = 8) respectively. To investigate the effects of raised [K+]o on the excitability of the neurosecretory terminals, stimulations were repeated in media of altered K+ concentration. The increase in [K+]o evoked by 6 Hz stimulation was elevated in 10 mM-K+ medium (133% of that in 5 mM-K+ medium) and reduced in 0 mM-K+ medium and in 25 mM-K+ medium. Thus it appeared that stimulus-induced changes in [K+]o might enhance the excitability of the tissue during electrical activation. 3. To test this hypothesis, we measured the field potential responses evoked by 0.5 Hz stimulation in media of different K+ concentrations. The size of the field potential was enhanced in 10 mM-K+ medium and depressed in 0 mM-K+ medium and in 25 mM-K+ medium. 4. Electrical stimulation (6 Hz, 1 min) decreased [Ca2+]o by 10.9 +/- 1.8% (n = 6). This decrease was absent in the presence of 1 microM-tetrodotoxin or 1 mM-cadmium. Again, the [Ca2+] response to stimulation was enhanced in 10 mM-K+ medium and depressed in 0 mM-K+ medium or 25 mM-K+ medium. 5. The release of vasopressin and oxytocin evoked by stimulation at 6 or 30 Hz from isolated neurohypophyses was measured by radioimmunoassay in a separate series of experiments. Stimulation at 30 Hz for 1 min released 5- to 6-fold more hormone than stimulation at 6 Hz for 5 min. Release evoked by 6 Hz stimulation was enhanced in 15 mM-K+ medium and depressed in 25 mM-K+ medium. 6. We conclude that the rise in [K+]o that accompanies high-frequency activation of axons and terminals in the neurohypophysis contributes to the facilitation of hormone release with increasing frequencies of stimulation, and in particular to the efficiency of the milk-ejection burst discharge of oxytocin neurones for evoking oxytocin release.
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PMID:Effects of raised extracellular potassium on the excitability of, and hormone release from, the isolated rat neurohypophysis. 340 69

Post-proline endopeptidase (PPE, EC 3.4.21.26) was purified 3,450 times from human lung. PPE was routinely assayed with the artificial substrate, carbobenzoxy-glycyl-L-prolyl-p-nitroanilide (Z-Gly-Pro-pNA). The pH optimum was 7.4, and the Mr was 77,000. Thiol blocking agents were strongly inhibitory but serine blocking agents were not inhibitory. No metal ions were required for activity, but heavy metal ions such as Hg2+, Cu2+, Cd2+, and Zn2+ completely inactivated the enzyme. Both dithiothreitol (DTT) and ethylenediaminetetraacetic acid (EDTA) were required to stabilize PPE activity. Michaelis constant values for Z-Gly-Pro-pNA and carbobenzoxy-glycyl-L-prolyl-2-naphthylamide were 0.36 and 0.10 mmol/l, respectively. PPE cleaved vasoactive peptides including bradykinin (BK) and des-(Arg9)-BK (Pro3-Gly4 and Pro7-Phe8 bonds), angiotensins I and II (Pro7-Phe8 bond), substance P (Pro4-Gln5 bond), and oxytocin (Pro7-Leu8 bond). Each of these peptides inhibited PPE-catalyzed hydrolysis of Z-Gly-Pro-pNA competitively. BK had the lowest Ki value (2.35 mumol/l) and oxytocin had the highest Ki value (84.0 mumol/l). PPE was not inhibited by captopril, a potent inhibitor of angiotensin converting enzyme, which also cleaves the Pro7-Phe8 bond of BK.
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PMID:Human lung post-proline endopeptidase: purification and action on vasoactive peptides. 354 26

Contractile effects of oxytocin, prostaglandin F2 alpha, acetylcholine, KCl, RbCl, and BaCl2 in the presence of Mn2+ and La3+ ions and other cations were studied in the rat myometrium at 37 degrees C. The effects depended mainly on the kind of the blocking agents (oxytocin in the presence of Mn2+ significantly increased muscle tone whereas in the presence of La3+, Cd2+, Mg2+ the effect was absent). The tone increase in the presence of Ca permeability blocking agents seems to be due to the effect of the agents on the intracellular sources of Ca ions.
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PMID:[Effect of stimulator substances on the contractile activity of the isolated rat myometrium against a background of various calcium permeability blockaders]. 624 89

With respect to recent reports suggesting an involvement of cadmium in preterm labor, the effects of this ion on the activity of myometrial strips from term pregnant women were examined. The interactions of cadmium with calcium and oxytocin on myometrial activity were also studied. Cadmium alone inhibited spontaneous contractile activity already in a concentration of 10(-9) M and in 10(-3) M myometrial contractions were almost completely abolished. Responses to Ca2+ and oxytocin were significantly increased by exposure to cadmium in low concentration (10(-9) M-10(-8) M), whereas higher concentration of Cd2+ had inhibitory action. These results suggest that cadmium not only blocks Ca2+ channels in the human myometrium, but also interferes with intracellular mechanisms involved in excitation-contraction coupling. The increased responses to Ca2+ and oxytocin in the presence of low amounts of Cd2+ support a role of cadmium in mechanisms of preterm labor.
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PMID:Effects of cadmium on myometrial activity of the nonpregnant human. Interactions with calcium and oxytocin. 790 May 19

A recent study demonstrated oxytocin (OT) receptors on hypothalamic cultured astrocytes (Di Scala-Guenot and Strosser, 1992). The attempt in the present paper was to determine a possible intracellular calcium mobilization induced by OT receptor activation in these cells. Using the microspectrofluorimetric technique with fura-2, as calcium indicator, brief applications of OT on single astrocytes induced a transient and reversible dose-dependent increase of intracellular calcium concentration ([Ca2+]i) in most of the cells tested. In a few cells, OT application triggered intracellular calcium oscillations. Repetitive applications of OT generally produced a decreasing calcium signal, suggesting a desensitization of the receptor. OT-induced calcium release was prevented by a prior or simultaneous application of an OT antagonist. The origin of the calcium mobilization was assessed during conditions where no extracellular calcium was available. Neither removal of extracellular calcium nor addition of a calcium channel blocker, cadmium 100 microM, in the bathing solution, did affect the calcium response to OT, demonstrating that release of intracellular calcium is solely involved in the OT-induced [Ca2+]i increase. The OT-induced calcium mobilization was abolished after thapsigargin application (100 nM). This indicates that the calcium response to OT application was principally associated with activation of the IP3-sensitive calcium stores. Taken together these results demonstrate that OT receptors previously detected on hypothalamic cultured astrocytes are functional receptors which transduction pathways involve calcium mobilization from IP3-sensitive stores.
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PMID:Increase of intracellular calcium induced by oxytocin in hypothalamic cultured astrocytes. 796 31


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